The synthetic cathinones are a class of drugs which have risen to popularity through their use as synthetic stimulants. Just as the synthetic cannabinoids have been marketed under the guise of “incense”, synthetic cathinones are commonly sold as “bath salts” or occasionally plant food, insect repellent, pond cleaner and vacuum freshener, all of which are often labelled as “not for human consumption”. They are available online and from local suppliers under a variety of names including Ivory wave, Cloud nine, Scarface, Vanilla sky, White lightning, Blizzard, Snow leopard, Red dove, Hurricane Charlie, Gravel and Blue silk. Synthetic cathinones and their derivatives are related to the naturally occurring alkaloid cathinone which is found in the Khat plant, Catha edulis and has mildly stimulating properties.
Synthetic cathinones are used to mimic the effects of cocaine and amphetamines and physical side-effects of these drugs include tachycardia, hypertension, arrhythmias, and seizures. They are also associated with a range of behavioural or mental-state effects including panic attacks, anxiety, paranoia, hallucinations and aggressive or violent behaviour. A number of deaths have also been linked to the use of “bath salts” (Marinetti & Antonides, 2013).
Since their rise as recreational drugs, governments around the world have taken actions to control synthetic cathinones. For example, in 2010, the UK government ordered a broad substituted cathinone ban in response to growing reports of mephedrone use. On 21 Oct. 2011, the Drug Enforcement Administration in the United States (DEA) finalized the temporary scheduling of mephedrone, methylone and MDPV (3′,4′-Methylenedioxy-α-pyrrolidopentiophenone) into schedule I under the Controlled Substances Act; in July 2012, this was made permanent.
Following the illegalization of these compounds, a second generation of synthetic cathinones emerged including alpha-pyrrolidinopentiophenone (RS)-1-phenyl-2-(1-pyrrolidinyl)-1-pentanone, hereinafter referred to as α-PVP). Between April and June 2013, α-PVP was the most prevalent drug in samples which tested positive on NMS labs Bath Salts Panel (NMS labs, 2013). In some countries, these fell under current legislation as analogues of banned compounds but in others, such as the USA, new bans had to be put in place. On Jan. 28 2014, the DEA temporarily listed α-PVP along with 9 other synthetic cathinones as Schedule I controlled substances; 4-methyl-N-ethylcathinone (“4-MEC”); 4-methyl-alphapyrrolidinopropiophenone (“4-MePPP”); 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butan-1-one (“butylone”); 2-(methylamino)-1-phenylpentan-1-one (“pentedrone”); 1-(1,3-benzodioxol-5-yl)-2-(methylamino)pentan-1-one (“pentylone”); 4-fluoro-N-methylcathinone (“4-FMC”); 3-fluoro-N-methylcathinone (“3-FMC”); 1-(naphthalen-2-yl)-2-(pyrrolidin-1-yl)pentan-1-one (“naphyrone”); and alpha-pyrrolidinobutiophenone (“α-PBP”).
A study on the metabolism of α-PVP in rats (Sauer et al., 2009) suggested the following routes; hydroxylation of the side chain followed by dehydrogenation to the corresponding ketone; hydrogenation of the 2′-position of the pyrrolidine ring followed by dehydrogenation to the corresponding lactam; degradation of the pyrrolidine ring to the corresponding primary amine; hydroxylation of the phenyl ring, most probably in the 4′ position; and ring opening of the pyrrolidine ring to the corresponding carboxylic acid.
Current analytical methods tend to use mass-spectrometry (MS) in conjunction with gas chromatography (GC) or liquid chromatography (LC) (Sauer et. al, 2009; Marinetti & Antonides, 2013). A disadvantage of such methods of detection is that they require expensive equipment and highly trained staff. On the other hand, immunoassays are known in the art as relatively cost effective, simplistic and rapid alternatives to MS based analysis. European patent number EP2626358 provides an immunoassay for detecting pyrrolidinophenones including MDPBP (3′,4′-Methylenedioxy-α-pyrrolinobutiophenone), naphyrone, MPVP (4-Methyl-α-pyrrolidinopentiophenone), MDPV and MDPPP (3′,4′-Methylenedioxy-α-pyrrolinopropiophenone) with very low cross-reactivity to α-PVP. Antibodies in EP2626358 are characterised having an IC50 value of greater than 20 ng/ml for each of the pyrrolidinophenones to which cross-reactivity is shown. There remains a need for an improved generic immunoassay which is not only more sensitive to the range of pyrrolidinophenone based compounds currently found in seized drugs, but that can also detect analogues and derivatives which may make their way onto the market in the future so as to enable improvements in the forensic, toxicological and clinical analysis of the intake of these ever evolving designer drugs.